Editorial: Exploring cutaneous drug-related and drug-associated adverse events: from clinical insight to therapeutic management

pembrolizumab for a triple negative breast cancer, while Didona et al. successfully used the antiinterleukin (IL)-4/IL-13 inhibitor dupilumab in a case series of 4 patients with ICIs-induced bullous pemphigoid, also identifying BP180 midportion as a specific autoantigenic target in this specific subset of patients.Dan Wang described a case of toxic epidermal necrolysis (TEN) following PD-1 inhibitor serlupimab administration for a small cells lung cancer (SCLC), focusing on the integrated multidisciplinary management with Western and Chinese nursing care and providing an interesting and educational perspective on the traditional Chinese medicine principles and practical approaches to skin diseases.Regarding Stevens-Johnson syndrome (SJS)/TEN spectrum -a rare but life-threating severe cutaneous records and performed a univariate analysis between in-hospital death (overall mortality 18.7%) and each SCORTEN parameter, showing that only tachycardia, malignancy and high serum urea remained independent predictors of mortality following multivariate regression analysis. These findings suggest that some SCORTEN parameters may be recalibrated to improve risk stratification in the current therapeutic context. The second most cited class of drug in our research topic articles was Janus Kinase inhibitors (JAKi), which represent a breakthrough in the treatment of inflammatory skin diseases. Both potential cutaneous side effects of JAKi and their use as a "rescue therapy" in drug-related skin AEs have been documented in our collection.Tang et al. conducted a retrospective disproportionality analysis using the US Food and Drug Administration Adverse Events Reporting System (FAERS) database on the association between oral JAK-1 inhibitors and infection risk in atopic dermatitis. Their findings confirmed the established association with herpetic infections and reactivations (e.g. herpes simplex and herpes zoster), pneumonia and influenza virus, but also suggested potential unlabelled association with sepsis and appendicitis, which requires further confirmation in real-life setting and independent studies.Regarding the infection risk of JAKi, we reported the case of a 53-year-old man with vitiligo who developed tinea faciei at the application site of ruxolitinib 1.5% cream, which eventually led to the permanent discontinuation of therapy (Romagnuolo et al.). Topical ruxolitinib represents a novel and effective topical JAK1/2 inhibitor approved for non-segmental vitiligo with a generally favourable safety profile: clinical trials only reported mild-to-moderate AEs including site-application acne, nasopharyngitis and site-application pruritus, although real-world data on infection risk are still lacking.JAKi site-application acne is also discussed in the timely and up-to-date review on acneiform drug A further contribution on biologics-adverse reaction has been reported by, Zhao et al., who performed a disproportionality analysis for evaluating the safety of the anti-IL-17A ixekizumab basing on the post-market report of AEs retrieved from the FAERS and VigiAccess databases. This study confirmed known AEs (e.g. fungal infections, injection site reactions, upper respiratory tract infections and inflammatory bowel diseases) but also potential association with other AEs such as cellulitis, herpes zoster, ear infection and diverticulitis, which warrant further real-world investigation.Xi et al. documented the occurrence of bullous pemphigoid in a 78-year-old woman affected by psoriasis following treatment with the anti-IL-23 guselkumab, while also performing a comparative single cell transcriptomic analysis on tissue samples of both diseases, in order to reveal distinctive cellular landscape and disrupted pathways associated with this reaction. In addition to novel and emerging treatment-related AEs, our research topic highlights 3 articles dedicated to topical steroids, which underscores their widespread use and valid role in current dermatological practice.Chen et al. reported a rare case of iatrogenic Cushing syndrome, likely induced by the abuse of topical clobetasol propionate over a 5-year for psoriasis treatment, suggesting that physician should remain vigilant regarding topical steroid therapies prescribed to patients, as well as monitoring the use of overthe-counter medications both for patients' safety and for a thorough anamnesis during clinical practice.On the similar subject of topical steroid abuse or "addiction", Myles et al. published a perspective on topical steroid withdrawal (TSW) syndrome, covering its history and varying definitions, as well as the academic scepticisms and controversies surrounding it. Furthermore, they outline current knowledge gaps in TWS and propose criteria to assist both patients and clinicians in recognizing this debated condition.Finally, a retrospective study on fifty-five male lichen sclerosus et atrophicus (LSA) of the genitalia has been proposed by Pessina et al. This study evaluated the effects of topical steroid versus circumcision on quality of life (QoL) and postoperative recurrence risk. The authors reported that topical steroids were not significantly associated with QoL improvement measured by dermatological life quality index (DLQI) compared to circumcision and that the median steroid-free survival after circumcision was 19 months. Nevertheless, they concluded that topical steroids remain a mainstay treatment across the various stages of LSA, emphasizing the need for a tailored treatment in LSA patients.Other contributions covering topics beyond those mentioned above reflect the broad spectrum of cutaneous drug reactions, especially in oncological patients. In conclusion, this Research Topic highlights how the shift toward targeted therapies and immunotherapies has redefined the landscape of cutaneous adverse events, introducing complex diagnostic challenges, but also opportunities for pathophysiological inquiry on drug-related skin adverse events. The evidence presented underscores the complexity of ICI-induced reactions and the dual role of JAK inhibitors as both potential triggers of adverse reaction and effective rescue therapies for biologic-induced paradoxical eruptions. Furthermore, the diverse cutaneous toxicities in oncological patients emphasize the need for a multidisciplinary and highly specialized management in this setting. Ultimately, integrating active pharmacovigilance with real-world clinical data is essential to optimizing therapeutic continuity and improving safety outcomes for patients receiving novel and targeted pharmacological agents.